Highly purified biologically active alpha-1-antitrypsins (alpha 1AT's) are being isolated from plasma using gel exclusion chromatography, Concanavalin A affinity chromatography, and DEAE ion exchange chromatography. Isolated preparations of alpha 1AT, trace-labeled with radioiodine, are being used to obtain data on the turnover of alpha 1AT in normal subjects, patients with alpha 1AT deficiency and their relatives and patients with chronic hepatocellular disease. The protease inhibitor phenotypes of subjects donating plasma for isolation of alpha 1AT and subjects undergoing alpha 1AT turnover studies are determined. Alpha 1AT's isolated from normal subjects (phenotype PiMM) and from patients with alpha 1AT deficiency (phenotype PiZZ) have different degrees of sialylation. Each is labeled with a different isotope of iodine and the metabolism of the two labeled preparations are compared in the same individuals. In addition, the metabolism in vivo of alpha 1AT which has been desialylated in vitro is being studied. The relationship between the degree of desialylation of alpha 1AT and its rate of catabolism and the extent to which decreased hepatic release or increased hepatic uptake of alpha 1AT contributes to the low plasma concentrations of alpha 1AT in alpha 1AT deficiency are being determined.